chr1-1020192-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_198576.4(AGRN):c.20C>T(p.Pro7Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,360,524 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_198576.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AGRN | NM_198576.4 | c.20C>T | p.Pro7Leu | missense_variant | 1/36 | ENST00000379370.7 | NP_940978.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AGRN | ENST00000379370.7 | c.20C>T | p.Pro7Leu | missense_variant | 1/36 | 1 | NM_198576.4 | ENSP00000368678 | P1 | |
AGRN | ENST00000620552.4 | c.-395C>T | 5_prime_UTR_variant | 1/39 | 5 | ENSP00000484607 |
Frequencies
GnomAD3 genomes AF: 0.0000198 AC: 3AN: 151144Hom.: 0 Cov.: 31
GnomAD4 exome AF: 0.00000662 AC: 8AN: 1209274Hom.: 0 Cov.: 29 AF XY: 0.00000506 AC XY: 3AN XY: 592316
GnomAD4 genome AF: 0.0000463 AC: 7AN: 151250Hom.: 1 Cov.: 31 AF XY: 0.0000812 AC XY: 6AN XY: 73908
ClinVar
Submissions by phenotype
Congenital myasthenic syndrome 8 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Mar 01, 2022 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 7 of the AGRN protein (p.Pro7Leu). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with AGRN-related conditions. This variant is not present in population databases (gnomAD no frequency). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at